The goals of the research are to better understand mechanisms of immunity, particularly T cell mediated immunity (CMI) against herpes simplex viruses (HSV) and how best to stimulate CMI with DNA free subunit vaccines. Mice will be immunized with HSV and at various times postinfection, their spleen cells will be stimulated in vitro with HSV or isolated glycoprotein antigens of HSV to generate cytotoxic T lymphocytes (CTL). Experiments are designed to establish which are the antigenic determinants of HSV that are principally responsible for inducing CTL and how to present these antigens for them to be maximally immunogenic. Liposomes containing different viral and transplantation antigens will be the major tool to answer these questions. Efforts will be made to establish the mechanism of cell and cell product interactions involved in the induction in vitro of anti HSV CTL. The nature of the viral determinants on virus infected target cells against which the CTL recognize and react will also be established. Experiments are planned in vivo to test the efficacy of glycoprotein subunit vaccines incorporated in liposomes to induce CMI as well as to suppress the severity or to eliminate clinical recrudescent disease in an experimental animal model. This research should reveal the antigens of HSV (ultimately type 1 and type 2) that stimulates CMI. Such information could prove useful to decide which antigens of HSV to include in DNA free subunit vaccines. The requirements for induction of CTL from human lymphocyte culture will be investigated and the specificity compared to murine anti-HSV CTL. Finally, investigations will be made to determine if the magnitude of induction or specificity of CTL generated in antigen stimulated human lymphocyte cultures is correlated with the frequency or severity of clinical herpes infections.